The overall objective of the research proposed in this application is to ascertain the regulatory effects of the corticosteroid hormones on the circulatory system, in particular the heart. The approaches taken to achieve this goal are to determine the circulatory consequences of adrenocortical insufficiency so that the primary circulatory locus of corticosteroid action is determined. Once this is known, studies will be directed toward an understanding of the subcellular and molecular mechanisms of this defect. This will allow further study on the mechanism of action of naturally occurring corticosteroid hormones on the circulatory system. In addition to investigating the normal physiological regulatory effects of corticosteroids on the circulatory system, studies will be devoted to determining the circulatory effects of pharmacological concentrations of corticosteroids in a variety of shock states (e.g., hemorrhagic, splanchnic ischemia, cardiogenic). These latter studies may lead to a better understanding of the site and mechanism of the protective effect of corticosteroids in shock. This will be of value in evolving a rational therapeutic regimen in various shock states. Finally, investigations will be undertaken to ascertain the effects of corticosteroids on myocardial performance and on myocardial cell integrity in acute myocardial ischemia and after acute myocardial infarction. This may offer insight into the pathophysiological mechanisms of these disease states as well as to provide therapeutic innovations in the treatment of acute myocardial ischemia and infarction.